Study finds hormones can change the breast's genetic material

Melbourne scientists Professor Jane Visvader (left) and Dr. Bhupinder Pal (right) have discovered how female steroid hormones can make dramatic changes to the genetic material in breast cells, changes that could potentially lead to breast cancer. The researchers are from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia. Credit: Walter and Eliza Hall Institute

Melbourne scientists have discovered how female steroid hormones can make dramatic changes to the genetic material in breast cells, changes that could potentially lead to breast cancer.

Researchers from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, have identified how pregnancy hormones send signals to critical molecules on the DNA to make changes in the epigenome. The epigenome is a series of chemical tags that modify DNA, controlling which genes are switched on and off.

Professor Jane Visvader, Dr Bhupinder Pal, Professor Geoff Lindeman and colleagues from the institute's laboratory led the study, which was published today in Cell Reports.

Professor Visvader said the researchers had created a roadmap of the of different breast cell types. In collaboration with Professor Gordon Smyth and colleagues from the institute's Bioinformatics division they determined how the epigenomes changed in response to ovarian hormones such as progesterone.

"We found the epigenome was very sensitive to hormonal regulation," Professor Visvader said. "This reveals another way in which female hormones can influence - by altering the epigenome through modifications in DNA tags."

The epigenome is where the DNA and the environment intersect, communicating signals from the outside world to the DNA. The epigenome doesn't alter the , but is a layer of proteins that sits 'on top' of the DNA and provides instructions on whether DNA should be read and 'switched on' to produce proteins.

The research team found that activate a molecule called EZH2, which is an important modifier of the epigenome. "We found that hormones including progesterone activate EZH2 to modify the epigenome, leading to global changes in the expression of a huge number of genes," Professor Visvader said.

"In normal tissue, EZH2 is essential for the development of including ducts and milk-producing cells, and for maintaining the activity of breast stem cells and their daughter progenitor cells. However, life-long exposure to hormones could lead to breast tumour initiation through increased levels of EZH2 and the changes that it orchestrates in the epigenome."

Breast cancer is the most common cause of cancer in women, accounting for almost 30 per cent of all cancers affecting women. One in nine women in Australia will develop breast cancer by the age of 85.

High levels of EZH2 are a marker of poor prognosis in breast cancer and have been frequently observed in basal-like breast cancers, the most aggressive types of breast cancer. "The link between progesterone, EZH2 and the epigenome, could be crucially important in the very early stages of breast cancer development," Professor Visvader said.

Professor Lindeman said there were decades of evidence linking hormone exposure with breast cancer, but the hormones' influence on the epigenome was not known. "Our discovery points to a role for -induced changes in the epigenome in the early stages of breast cancer initiation, and could lead to new therapeutics for treating breast cancer," Professor Lindeman said. "Inhibitors against EZH2 are being developed by others, but it will be several years before we know the outcome of these on cancer."

Related Stories

Stem cell 'daughters' lead to breast cancer

Aug 02, 2009

Walter and Eliza Hall Institute scientists have found that a population of breast cells called luminal progenitor cells are likely to be responsible for breast cancers that develop in women carrying mutations ...

Recommended for you

Growing a blood vessel in a week

Oct 24, 2014

The technology for creating new tissues from stem cells has taken a giant leap forward. Three tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days. This is shown ...

Testing time for stem cells

Oct 24, 2014

DefiniGEN is one of the first commercial opportunities to arise from Cambridge's expertise in stem cell research. Here, we look at some of the fundamental research that enables it to supply liver and pancreatic ...

Team finds key signaling pathway in cause of preeclampsia

Oct 23, 2014

A team of researchers led by a Wayne State University School of Medicine associate professor of obstetrics and gynecology has published findings that provide novel insight into the cause of preeclampsia, the leading cause ...

Rapid test to diagnose severe sepsis

Oct 23, 2014

A new test, developed by University of British Columbia researchers, could help physicians predict within an hour if a patient will develop severe sepsis so they can begin treatment immediately.

User comments